The quest to map STIM1 activation in granular detail

IF 4.3 2区 生物学 Q2 CELL BIOLOGY Cell calcium Pub Date : 2024-08-23 DOI:10.1016/j.ceca.2024.102946
Patrick G Hogan
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Abstract

The conformational change in STIM1 that communicates sensing of ER calcium-store depletion from the STIM ER-luminal domain to the STIM cytoplasmic region and ultimately to ORAI channels in the plasma membrane is broadly understood. However, the structural basis for the STIM luminal-domain dimerization that drives the conformational change has proven elusive. A recently published study has approached this question via molecular dynamics simulations. The report pinpoints STIM residues that may be part of a luminal-domain dimerization interface, and provides unexpected insight into how torsional movements of the STIM luminal domains might trigger release of the cytoplasmic SOAR/CAD domain from its resting tethers to the STIM CC1 segments.

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绘制 STIM1 激活细节图的探索
STIM1 的构象变化可将ER钙库耗竭的感知从 STIM ER 管腔结构域传递到 STIM 细胞质区域,并最终传递到质膜上的 ORAI 通道。然而,STIM 管腔域二聚化驱动构象变化的结构基础却被证明是难以捉摸的。最近发表的一项研究通过分子动力学模拟解决了这一问题。报告指出了可能是腔域二聚化界面一部分的 STIM 残基,并对 STIM 腔域的扭转运动如何触发细胞质 SOAR/CAD 域从其与 STIM CC1 段的静止系链中释放提供了意想不到的见解。
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来源期刊
Cell calcium
Cell calcium 生物-细胞生物学
CiteScore
8.70
自引率
5.00%
发文量
115
审稿时长
35 days
期刊介绍: Cell Calcium covers the field of calcium metabolism and signalling in living systems, from aspects including inorganic chemistry, physiology, molecular biology and pathology. Topic themes include: Roles of calcium in regulating cellular events such as apoptosis, necrosis and organelle remodelling Influence of calcium regulation in affecting health and disease outcomes
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